We have developed a system to study the changes in gene expression in CD4+ T lymphocytes that occur during human immunodeficiency virus (HIV) infection. Using mRNA differential display, we catalogued a number of genes which are differentially expressed between the human T-cell line A3.01, and its persistently HIV-infected daughter line, ACH-2. We have begun to exploit this technology to identify cellular genes whose expression is dysregulated upon acute infection of primary peripheral blood CD4+ T cells with a primary viral isolate; we will also investigate the expression of candidate genes in lymph nodes of HIV-infected individuals. Ongoing work is aimed at verification/analysis of apparently affected genes to ascertain their role in HIV pathogenesis/immune dysregulation. These studies will enable us to dissect, at the molecular level, the mechanism of HIV-induced immune dysfunction.